Human rotavirus (HRV) is the most common cause of diarrhea among infants and young children. Worldwide, including Korea, nearly 95% of children have been infected with the virus at least once by the age of 5, and it is known to account for ˜40% of about 125 million diarrhea patients occurring every year. Hence, rotavirus is a very important pathogen in public health (Patel et al. 2011. Pediatr Infect Dis J 30: S1-S5). The virus is non-enveloped and is surrounded by a three-layered icosahedral protein capsid 75 nm in diameter, consisting of an outer capsid, an inner capsid and a core protein. It is known as a dsRNA virus consisting of 11 segments. Each segment codes for one of 6 structural proteins (VP1, VP2, VP3, VP4, VP6 and VP7) and 6 nonstructural proteins (NSPs 1-6) (Estes and Cohen, 1989. Rotavirus gene structure and function. Microbiol Rev 53: 410-449). Rotavirus is classified into 7 groups, from A through G, depending on the antigenicity of VP6. Group A rotaviruses, which are the most common globally, may be subdivided into glycoprotein type (G type) by the immunogenic protein VP7 and protease-sensitive type (P type) by VP4. At present, 23 G types and 32 P types are reported. In human, 9 serotypes including G1-G4, G6, G8-G10 and G12 and 8 genotypes including P[3], P[4], P[6], P[8]-P[11] and P[14] cause infections. The serotypes are not cross-protective (Banyai et al. 2009. Arch Virol 154: 1823-1829; Matthijnssens et al., 2009. Future Microbiol 4: 1303-1316).
According to the Centers for Disease Control and Prevention (CDC) of the US, annual cost spent for the treatment of rotavirus-associated diarrhea amounts to 10 million dollars in the US only. In Korea, 70% of infants and young children hospitalized for acute enteritis are those who are infected by the virus. Accordingly, the World Health Organization (WHO) is striving to reduce occurrence of rotavirus in developing countries and to develop vaccines against rotavirus in developed countries to save medical cost (Parashar et al. 2003. Emerg Infect Dis 9:565-572).
Meanwhile, infection with human hepatitis A virus (HAV) is increasing recently in the western part of the US, the Middle East and some regions in Asia. The spread of hepatitis A is a global concern. Also in Korea, hepatitis A is rapidly increasing in recent years in teenagers and those who are in their twenties who lack immunity against the virus. The infection is commonest in ages between 5 and 14 years. It is reported that about 30% of patients are aged 15 or younger. According to a survey in the US from 1982 through 1993, the incidence of hepatitis A (47%) was more frequent than hepatitis B (37%), and serologic test revealed that about 33% of the US population had been infected with hepatitis A virus (Gust et al. 1992. Vaccine 10: S56-S8). Hepatitis A virus is an RNA virus belonging to the family Picornaviridae, around 27 nm in diameter. After an incubation period of 28 days on average, it can induce acute liver disease characterized by such clinical symptoms as fever, malaise, appetite loss, nausea, abdominal pain, dark urine, jaundice, etc. Like rotavirus, it is non-enveloped and contains a single-stranded 7.5-kb RNA packaged in an icosahedral protein shell 27 nm in diameter. It is known to have one long ORF (P1-3) (Totsuka et al. 1999. Intervirology 42: 63-68).
Hepatitis A is mainly spread by the fecal-oral route, like rotavirus, via contact with contaminated food or drinking water. About 11-22% of hepatitis A patients are hospitalized. When an adult patient is hospitalized, he/she will have to be away from work for about 27 days. When the disease outbreaks, a preventive therapy is required for 11 people who contacted with the patient on average. In the US, the direct and indirect costs spent for one hepatitis A patient is estimated at 1,817-2,459 dollars for an adult and 433-1,492 dollars for one who is aged 18 or younger (WHO. 2000. MMWR Wkly Epidemiol Rec 75: 38-44). In Korea, hepatitis A is increasing rapidly nationwide, centered around the metropolitan areas including Seoul, Incheon and Gyeonggi. According to an epidemiological study by the Korea Centers for Disease Control and Prevention, the outbreak of hepatitis A is increasing quickly, with 2,233 cases in 2007 and 1,575 cases between January and June of 2008 (KCDC, 2010).
Throughout the specification, a number of publications and patent documents are referred to and cited. The disclosure of the cited publications and patent documents is incorporated herein by reference in its entirety to more clearly describe the state of the related art and the present disclosure.